Abstract
Proteasome inhibitors represent potential novel anti-cancer therapy. These agents inhibit the degradation of multi-ubiquitinated target proteins mediating cell cycle progression, apoptosis, NF-kappa B activation, inflammation, cell cycle regulatory proteins such as cyclins and cyclin dependent kinase inhibitors, as well as immune surveillance; and regulate anti-apoptosis and cell cycle progression. Proteasome inhibitors also directly induce caspase-dependent apoptosis of tumor cells, despite the accumulation of p21 and p27 and irrespective of the p53 wild type or mutant status. Recent studies demonstrate that PS-341, peptide boronate, has remarkable anti-tumor activity in preclinical and clinical studies, not only in multiple myeloma but also in other malignancies.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Apoptosis / drug effects
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Boronic Acids / pharmacology
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Boronic Acids / therapeutic use
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Bortezomib
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Cell Adhesion / drug effects
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Cysteine Endopeptidases
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Cysteine Proteinase Inhibitors / pharmacology*
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Cysteine Proteinase Inhibitors / therapeutic use
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Hematologic Neoplasms / drug therapy*
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Hematologic Neoplasms / enzymology
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Hematologic Neoplasms / pathology
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Humans
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Multienzyme Complexes / antagonists & inhibitors*
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Neovascularization, Pathologic / drug therapy
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Proteasome Endopeptidase Complex
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Pyrazines / pharmacology
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Pyrazines / therapeutic use
Substances
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Boronic Acids
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Cysteine Proteinase Inhibitors
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Multienzyme Complexes
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Pyrazines
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Bortezomib
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex